Background. Stress and exposure to drug-related cues (environmental stimuli previously associated with drug availability) are considered factors that increase the risk of relapse to heroin and/or cocaine use. The two factors may act through different neural mechanisms. Alpha-2 adrenergic agonists, such as clonidine, have been shown to block stress-induced relapse, but not cue-induced relapse, to heroin and cocaine self-administration in rodents. The ability of clonidine to attenuate stress- or cue-induced heroin and cocaine craving in drug abusers has not been tested. It is important to determine, in humans, whether clonidine blocks the acute effects of only one putative class of relapse precipitants, or whether its effects are more general.